Geriatric PK Flashcards
Why are older adults a special population?
health:
-heterogenous population
-aging process is unpredictable
-multiple simultaneous disease states
-chronic illness
changing demographics:
-population composition, institutionalization
epidemiology of drug use in the older adult:
-polypharmacy
-underuse of potentially beneficial therapy
drug effect:
-3 to 10 fold greater ADRs
available PK/PD information:
-evidence based for prescribing in older adults is limited
-clinical studies not representative of older adult population
What do age-related changes in organ function impact?
alters drug PK and PD resulting in alterations in pharmacological response
True or false: physiological aging correlates with chronological aging
false
physiological aging does not necessarily correlate with chronological aging
Are age-related changes themselves enough to compromise normal function?
age-related changes in-of-themselves are often not sufficient to compromise normal function
-however with underlying pathological conditions (e.g. HF, renal decline). such age-related changes may have significant consequences on PK/PD
What are the changes in body composition with aging?
decreased total body water; decreased ICF volume
decreased lean body mass and increased body mass
no change or decrease in serum albumin
no change or increase in serum AAG
What are the cardiovascular changes with aging?
decreased myocardial sensitivity to B-adrenergic stimulation
decreased baroreceptor activity
decrease CO; decreased resting HR
increased systemic vascular resistance; increased SBP
What are the CNS changes with aging?
decreased weight and volume of the brain
decreased cerebral blood flow
increased BBB permeability
alterations in cognition
What are the endocrine system changes with aging?
thyroid gland atrophy
menopause
decrease testosterone
increased incidence of diabetes and thyroid disease
What are the fluid/electrolyte changes with aging?
increased electrolyte abnormalities
What are the GI system changes with aging?
no change or sometimes increased gastric pH
delayed gastric emptying
decreased splanchnic blood flow; decreased intestinal rate
decreased absorptive surface (mucosal atrophy)
no change passive intestinal permeability; decreased active nutrient transport
What are the GU system changes with aging?
increased incidence of UI
What are the immune system changes with aging?
decreased cell-mediated immunity
What are the liver changes with aging?
decreased liver size and number of hepatocytes
decreased liver blood flow
? oxidative and conjugative metabolism
What are the MSK changes with aging?
increased cartilage breakdown in joints
increased bone porosity; decreased BMD
decreased muscle size and mass; decreased peripheral neurons
What are the nutrition changes with aging?
possible protein energy malnutrition
increased anorexia and micronutrient deficiences
What are the pulmonary system changes with aging?
decreased respiratory muscle strength and chest wall compliance
decreased total alveolar surface
decreased vital capacity
What are the renal system changes with aging?
decreased GFR; decreased renal blood flow
increased tubular atrophy and decreased tubular secretory function
decreased compensatory acid-base and electrolyte balance
decreased renal mass and increased fibrosis and arterosclerosis
What are the sensory changes with aging?
decreased accommodation of the lens of the eye
decreased visual and auditory acuity
What are the integument changes with aging?
increased dryness, wrinkles; decreased # hair follicles and melanocytes
increased epithelial thinning and loss of dermal thickness
decreased wound healing and thermoregulation
decreased vitamin D function and increased photosensitivity
What does Css depend on?
Css = F x dose/Cls
What does t1/2 depend on?
t1/2 = 0.693 x Vd/Cls
What do age-related changes in GIT absorption lead to?
impaired/delayed drug absorption as rate and/or extent of absorption is altered
-usually clinically irrelevant
What is an important GI change in PK?
may see decreased 1st pass effect = increased F for high Eh drugs
What is Vd influenced by?
age-related changes in:
-body composition
-blood flow rates
-binding to biologic material
Describe the PK changes in distribution seen with aging.
decreased Vd and increase Cp of water soluble drugs
increased Vd and increased t1/2 if fat soluble drugs
increased or decreased or no change in fub of highly PPB drugs
-increased fub for drugs bound to albumin
-decreased fub for drugs bound to AAG
if Vd increased then t1/2 increased and should increase dosing interval
Which phase of metabolism is impacted by aging?
phase 1 more affected
limited alterations in phase 2 metabolism
What is the effect of aging on Clint?
Clint associated with extensive interindividual variability; therefore it is difficult to assess the effect of age on hepatic drug metabolizing activity
Describe the PK changes in metabolism seen with aging.
decreased Cls and increased t1/2 for some low Eh drugs
decreased Qh and decreased Clh for high Eh drugs
Why is SCr misleading in older patients?
decreases in GFR with age may be matched by decreases in muscle mass and urinary excretion of creatinine
Which renal parameters decline with age?
RBF
GFR
tubular secretion
Describe the PK changes seen in excretion with aging.
decreased Cls and increase t1/2 of renally eliminated drugs
increased t1/2 and increased time to reach SS
When are changes to the LD needed?
when changes to Vd
When are changes to the MD needed?
when changes in Cls to maintain Css
When are changes to dosing interval needed?
Vd influences t1/2 which influences time to reach SS
Cls influences t1/2 which influences time to reach SS
What is the effect of age on drug response?
effect of age on the sensitivity to drugs varies with the studied and response measured
-older adults may have a greater or reduced response at a given Cp vs young adult
Which body systems do we primarily see age-dependent changes in PD?
CV and neuroendocrine
-more sensitive to BZDs, narcotics, anticoagulants, antihypertensives
-increased NSAID adverse effects
Why do older adults have altered drug responses?
altered homeostatic responses to drugs and altered drug responses induced by chronic disease
age-related changes in PD not easily predicted; titrate dose according to response
What are the common interactions with aging?
drug-drug interaction
drug-nutrition interaction
drug-disease interaction
